Immunotherapy of cancer involving adoptive transfer of T cells for various human tumor antigens has significantly improved in recent years. It has also recently become clear that immunotherapy is more potent if both the innate and the adaptive cellular immune responses are efficiently engaged. Timely recognition of the tumor by the cells of the innate immune system, such as NK cells, granulocytes, and macrophages, appears to be a prerequisite for an efficient stimulation of tumor-specific adaptive immunity.
Tumor-specific antibodies have been transduced into T cells (T-bodies) endowing the transduced T cells with MHC-unrestricted tumor antigen specificity. While antibodies can have exquisite specificity, one disadvantage is their high affinity of binding to antigen, which could impair infiltration of tumors, result in irreversible binding of an effector cell to a tumor cell, and possibly result in apoptosis of effector cells following their interaction with tumor cells. T cell receptors (TCRs), however, have a much lower binding affinity. Therefore, a cell bearing a tumor-specific TCR could engage and disengage from its target multiple times and effect its function against multiple tumor cells. Tumor specific T cells, however, are MHC-restricted. Accordingly, a tumor specific T cell is effective only for treatment of patients having a suitable human lymphocyte antigen (HLA). Additionally, tumor cells frequently down-regulate MHC or antigen processing molecules, thereby avoiding T cell recognition. Despite these limitations, adoptive immunotherapy therapies involving transfer of tumor-specific TCRs into T cells continue to be developed. Accordingly, the art is in need of an adoptive immunotherapy that can treat or prevent cancer in most or all patients. Desirably, such a therapy would not be dependent on the HLA or antigen processing components of target cancer cells. Moreover, it would be desirable if such a therapy caused little or no immune reaction with non-target cells.